Carvalho-Pinto Carla, García María I, Gómez Lucio, Ballesteros André, Zaballos Angel, Flores Juana M, Mellado Mario, Rodríguez-Frade José Miguel, Balomenos Dimitrios, Martínez-A Carlos
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM Campus de Cantoblanco, Madrid, Spain.
Eur J Immunol. 2004 Feb;34(2):548-57. doi: 10.1002/eji.200324285.
Lymphocyte infiltration to pancreatic islets is associated to chemoattraction, as are other inflammatory autoimmune processes. We examined whether development of insulitis and diabetes depends on chemoattraction of lymphocytes via the CCR5 chemokine receptor. In non-obese diabetic (NOD) mice, a substantial fraction of peripheral T cells and virtually all B cells expressed high CCR5 levels. CCR5 expression characterized the effector T cell phenotype, suggesting their potential involvement in disease development. In view of these findings and the CCL5 (RANTES, the CCR5 ligand) expression by pancreatic islets, we treated NOD mice with a neutralizing anti-CCR5 antibody. This did not influence peri-insulitis advancement, but inhibited beta-cell destruction and diabetes. These data demonstrate a role of CCR5-dependent chemoattraction in insulitis progression to islet destruction, suggesting the potential value of therapeutic intervention by CCR5 targeting.
淋巴细胞浸润胰岛与化学趋化作用相关，其他炎症性自身免疫过程也是如此。我们研究了胰岛炎和糖尿病的发展是否依赖于通过CCR5趋化因子受体的淋巴细胞化学趋化作用。在非肥胖糖尿病（NOD）小鼠中，相当一部分外周T细胞以及几乎所有B细胞均高表达CCR5。CCR5表达是效应T细胞表型的特征，表明它们可能参与疾病发展。鉴于这些发现以及胰岛表达CCL5（调节激活正常T细胞表达和分泌因子，CCR5配体），我们用中和性抗CCR5抗体治疗NOD小鼠。这并未影响胰岛周围炎的进展，但抑制了β细胞破坏和糖尿病。这些数据证明了CCR5依赖性化学趋化作用在胰岛炎进展为胰岛破坏中的作用，提示了靶向CCR5进行治疗干预的潜在价值。
